Expression Profile of Diabetes-Related Genes Associated with Leukocyte Sirtuin 1 Overexpression in Gestational Diabetes

Abstract

Although compelling evidence indicates that Sirtuin 1 (SIRT1) plays a prominent role in type 2 diabetes, its relationship with gestational diabetes (GDM) remains elusive. This study was aimed at identifying diabetes-related genes and cellular pathways linked to changes of leukocyte <i>SIRT1</i> expression at the time of GDM diagnosis. For this purpose, 122 GDM patients were screened for leukocyte <i>SIRT1</i> expression, and two subgroups were distinguished, namely GDM/<i>SIRT1</i>(↑) (<i>n</i> = 30, <i>p</i> < 0.05) and GDM/<i>SIRT1</i>(↔) (<i>n</i> = 92, <i>p</i> > 0.05), with significant and insignificant changes in leukocyte <i>SIRT1</i> expression compared to a normal glucose tolerant (NGT) group (<i>n</i> = 41), respectively. PCR array analysis identified 11 diabetes-related genes with at least a ± 2-fold difference in expression in GDM/<i>SIRT1</i>(↑) patients (<i>n</i> = 9) vs. NGT controls (<i>n</i> = 7); in addition, significant differences in the expression of four of the six investigated genes were confirmed between the entire GDM/<i>SIRT1</i>(↑) group and the whole NGT group (<i>p</i> < 0.05). Interestingly, of these four genes, only <i>ACLY</i> expression was found to significantly differ between GDM/<i>SIRT1</i>(↑) and GDM/<i>SIRT1</i>(↔). This study demonstrates that under hyperglycemic conditions, leukocyte <i>SIRT1</i> overexpression is accompanied by an over-abundance of three transcripts and an under-abundance of another; these four govern related metabolism, inflammation, and transport functions, suggesting that such alterations might represent systemic biological adaptations with a unique <i>ACLY</i> under-expression in GDM/<i>SIRT1</i>(↑) women.